Extracellular ischaemia markers in repeated global ischaemia and secondary hypoxaemia monitored by microdialysis in rat brain

The aim of this study was to explore the usefulness of extracellular markers of cerebral ischaemia. Cortical microdialysate concentrations of the energy related metabolites lactate, pyruvate, glucose, adenosine, inosine, hypoxanthine and xanthine, were measured in rats subjected to repeated transient ischaemia. The animals were subjected to one or two 10-min periods of global ischaemia produced by induced intracranial hypertension, with a 2 h period of reperfusion after each insult. In addition, the effect of superimposed secondary hypoxaemia and hypotension was studied. In general, there was a good agreement between the extracellular markers and known intracellular energy disturbances under similar conditions, including marked transient increases of lactate, lactate/pyruvate ratio, inosine and hypoxanthine. Several new observations were made: (1) glucose appeared to be a useful marker of severe ischaemia and recirculation, (2) a marked post-ischaemic xanthine formation was observed implicating a substantial loss of salvageable hypoxanthine as well as increased production of superoxide radicals, (3) a blunted purine response was noted after the second insult, reflecting a reduced intracellular adenine nucleotide pool, and (4) a different pattern of ischaemia markers was observed during secondary hypoxia as compared to hypoxia with hypotension. In conclusion, extracellular lactate, pyruvate, glucose, adenosine, inosine hypoxanthine and xanthine all seem valuable as ischaemia markers. The results support the usefulness of intracerebral microdialysis for monitoring of energy metabolic disturbances caused by cerebral ischaemia/hypoxia. The pattern of extracellular ischaemia markers may help differentiate between various causes of energy perturbations, such as different degrees of ischaemia and hypoxia.